Polygenic risk, population structure and ongoing difficulties with race in human genetics.
Polygenic risk, population structure and ongoing difficulties with race in human genetics.
复制标题
多基因风险，人口结构和人类遗传学中种族的持续困难。
DOI：
10.1098/rstb.2020.0427
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发表时间：
2022-06-06
影响因子：
6.3
通讯作者：
Fullerton, Stephanie M.
中科院分区：
文献类型：
--
作者：
Kaplan, Jonathan Michael;Fullerton, Stephanie M.
关键词：
无论是在人类种群遗传学领域，还是在科学公共传播的史册上，《人类多样性的分配》都是一个值得注意的干预。尽管列文丁的结论被广泛接受，即种族分类几乎没有遗传或分类学意义，但生物医学研究界仍在努力解决是否以及如何在其工作中最好地考虑种族问题。在将与复杂疾病风险相关的基因以多基因风险评分(PR)的形式转化为临床应用的最新尝试中，这种斗争最为明显。在这篇透视文章中，我们追踪了目前围绕在不同患者队列中适当开发和临床应用PR的挑战，以及持续存在的困难，以确定人口结构的哪些方面对人类健康至关重要，以及出于什么原因。尽管有许多分析创新，但从列文丁的工作中出现的一些理由仍然令人怀疑，在多基因风险估计的背景下考虑人口结构将使我们能够更有效地识别和干预困扰世界各地边缘化人口的显著健康差距。这篇文章是《庆祝列文廷对人类多样性的分配50周年》主题的一部分。
‘The Apportionment of Human Diversity’ stands as a noteworthy intervention, both for the field of human population genetics as well as in the annals of public communication of science. Despite the widespread uptake of Lewontin's conclusion that racial classification is of ‘virtually no genetic or taxonomic significance’, the biomedical research community continues to grapple with whether and how best to account for race in its work. Nowhere is this struggle more apparent than in the latest attempts to translate genetic associations with complex disease risk to clinical use in the form of polygenic risk scores, or PRS. In this perspective piece, we trace current challenges surrounding the appropriate development and clinical application of PRS in diverse patient cohorts to ongoing difficulties deciding which facets of population structure matter, and for what reasons, to human health. Despite numerous analytical innovations, there are reasons that emerge from Lewontin's work to remain sceptical that accounting for population structure in the context of polygenic risk estimation will allow us to more effectively identify and intervene on the significant health disparities which plague marginalized populations around the world. This article is part of the theme issue ‘Celebrating 50 years since Lewontin's apportionment of human diversity’.
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DOI：
10.1126/science.1193032
发表时间：
2010-08-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Genovese G;Friedman DJ;Ross MD;Lecordier L;Uzureau P;Freedman BI;Bowden DW;Langefeld CD;Oleksyk TK;Uscinski Knob AL;Bernhardy AJ;Hicks PJ;Nelson GW;Vanhollebeke B;Winkler CA;Kopp JB;Pays E;Pollak MR
通讯作者：
Pollak MR
影响因子：
12.3
作者：
Rotimi C;Shriner D;Adeyemo A
通讯作者：
Adeyemo A
影响因子：
14.9
作者：
Buniello, Annalisa;MacArthur, Jacqueline A. L.;Parkinson, Helen
通讯作者：
Parkinson, Helen
影响因子：
64.5
作者：
Belbin, Gillian M.;Cullina, Sinead;Kenny, Eimear E.
通讯作者：
Kenny, Eimear E.
影响因子：
16.6
作者：
Duncan, L.;Shen, H.;Domingue, B.
通讯作者：
Domingue, B.